New Mexico (NM) is the only state with the capacity to fully monitor cervical cancer screening and human papillomavirus (HPV) prevention using a state-wide woman-based electronic informatics system under mandated reporting. We are uniquely positioned to address gaps in understanding HPV vaccine impact and effectiveness within a mulit-cultural US population suffering many disparities. Our project will accomplish three integrated specific aims required to provide definitive baseline characterizations of the opportunistic cervical cancer screening program in NM. In Aim 1, we will establish the individual HPV genotype distribution of 37 HPV genotypes needed to appropriately monitor expected or unexpected population-based impact of HPV vaccines. Although we have performed a state-wide sampling of over 60,000 cervical samples targeting all women with abnormal Pap tests and a random sample of women with normal Pap tests, our existing resources were limited to HPV genoytping of 40,000 samples. In this Aim we will achieve the targeted sample size by performing the additional 20,000 HPV genotype assays.We will describe the agespecific population-based genotype distribution and determine the genotype-specific risk for CIN2+ outcomes across the 2 year grant period. In Aim 2, we will convene a pathology panel to determine consensus diagnoses for ~8,000 cervical biopsies including >CIN/AIS. The consensus diagnoses will be compared to community-based diagnoses determined for the same specimens through use of the NM HPV Pap Registry (NMHPVPR) data warehouse. We will create a gold standard slide set that will enable standardization of future population-based assessments, a prerequisite for determining the real-world impact and effectiveness of HPV vaccination. In Aim 3 we will develop a shared image resource of the cervical biopsy tissues and validate the use of image-based versus glass-based diagnoses. Because the impact of HPV vaccines is expected to increase over time, longitudinal periodic assessments will be expected to span several decades. Image-based diagnostic standards will be critical to future population evaluations.